Process of preparing n-brominated halogen compounds



United States Patent PROCESS OF PREPARING N-BROMINATED HALOGEN COMPOUNDSLaurene 0. Paterson, Adrian, Mich., assignor to Drug Research, Inc.,Adrian, Mich., a corporation oliMichigall No Drawing. Application August6, 1956 Serial No. 602,466

4 Claims. (Cl. 260-248) This invention relates to new methods ofpreparing organic halogen carriers and specifically relates to newmethods of preparing organic halogen carriers containing bromine aloneor both chlorine and bromine and is directed particularly to the classof halogen carriers characterized as N-halogen compounds.

Generally, the class of compounds which may be prepared by the presentprocess are characterized as halogenating agents containing at least oneN-halogen radical in which structure .the halogen atom is loosely boundto the nitrogen atom and is readily available for chemical reaction.Specifically, the products produced by this process arethose whichcontain at least one N-bromo radical and may also contain additionalN-bromo or N-chloro groups. Thus compounds such as N-bromo succinimide,N-bromo phthalimide, N-bromo-cyanuric acids, N-bromo melamines,N,N-dibromo-S-substituted hydantoins, N- brorno-toluene-sulfonamide,N-bromo-3a,6a-substitutedglycolurils, N-bromo-S-substituted barbituratesand .the like are contemplated as products which may be prepared by thisprocess. In addition, one may also prepare the mixeddihalo-(N-bromo-N-chloro) compounds where more than a single nitrogenatom is in the carrier molecule, such as for example,N-chloro-N-bromo-S-substituted hydantoin.

The compounds which are particularly preferred as N- halogen carriersare classified as N-cyclic imides and are represented by the hydantoins,succinimide, phthalimide, cyanuric acid, the glycolurils, and the like.I

The properties and methods of manufacture for many of these compoundshave been described in the chemical literature: N-bromoacetamide,Behrend and Schreider, Ann. 318, 373 (1901), N-bromo succinimide,Ziegler, Ann. 551, 109 (1942),. N-monoand N-N-dibromodimethyl hydantoin,Orazi, Anales, Asociacion Quemica Argentina, vol. 37, 192 (1949), andvol. 38, 5 (1950). In the preparations as described, the carrier isusually reacted in alkaline medium with bromine, and the N- brominatedcompound isolated in a solid crystalline form.

Halogen carriers which contain both bromine and chlorine are also known,being described in my copending application Serial No. 438,633, filedJune 22, 1954, now U; S. Patent No. 2,779,764.. That prior applicationdescribes methods of preparing N-bromo-N-chloro-S-substituted hydantoinsand N,N-dibromo-S-substituted hyd'antoins. a

'Generally, the methods employed in the prior art to prepare theseN-brominated carrier compounds comprise reaction of the unsubstitutedcarrier with elementary bromine in an aqueous alkaline media. In such areaction one-half of the bromine molecule (Brsubstitutes for thehydrogen atom in the NH radical andthe remainder combines with thathydrogen atom to form hydrogen bromide (HBr). This acid then reacts withthe alkali present to form the alkali bromine salt as a by-product. Thecarrying out of this reaction by these prior art methodsjis sometimesrendered difficult since the carrier compounds. areoften. adversely.affected by strongly alkaline conditions and localized areas of highbromine concentration.

The following equation will illustrate the preparation of N-bromosuccinimide from succinimide by this prior art process:

II C Biz-C NH Bra NaOH O CHr-(ii U NBI NaBr 11 0 's-C ii u) bromohalogen carriers which employs mild reaction conditions.

A further object is to provide a process for preparing N.-bromo halogencarriers which may be carried out in the absence of strong base.

A further object is to provide a process for preparing N-halogencarriers which does not employ elementary 'bromine..

A still further object is to provide a process for making mixedN-bromo-N-chloro halogen carriers.

Further and additional objects will appear from the followingdescription and the appended claims.

In one broad aspect of this invention there is provided a processforpreparing N-bromo halogen carriers containing only bromine whichcomprises treating an N- chloro organic nitrogen compound with a bromineproducing compound such as a bromide. Generally the organic nitrogencompounds which are suitable starting materials to prepare the N-bromoderivatives are N- chloro organic nitrogen compounds containing at leastone radical selected from the group consisting of:

The bromine producer may be a bromide such as a bromine salt of thecharacter of sodium bromide, potassium bromide, and the like. Theprocess of the present invention may be carried out in an aqueous media,or if desired may be carried out in inertorganic solvents such asheptane, hexane, carbon tetrachloride, and the like.

The amount of bromine producer or bromide which is utilized in thisparticular embodiment of the process should be at least one equivalentof bromide for each replacement of a removable chlorine atom containedin the I N'Cl radicals in one mole of the halogen carrier start- 1 ingmaterials. Thuswhere a carrier starting material con-' tains buta-single N-Cl group an equivalent of a brornide-such asNaB'r (or-onemole) would be required per mole of "starting material. Similarly, wherethe carrier startingmaterial contains two N-chloro'groups, two

equivalents of bromide are required per mole of carrier startingmaterial.. Thus, to produce an N,N-dibromo-- substituted hydantoin,onewould react one mole of N,N dichloro-S-substituted hydantoin with atleast-two-moles of a bromidesuch as.N-al3r. if a divalent salt such asCaBr were used, two equivalents or one mole would be required.

The overall process may be exemplified by the following equation:

As may be seen from the above equation, this particular embodimentresults in the production of an N-bromo halogen carrier without the useof elementary bromine or alkali. It is also apparent thatall of thebromide reactant is utilized and the only by-product is the low costNaCl.

It is also contemplated as an embodiment of this present.

process the production of N-bromo halogen carriers wherein the carriersalso contain unsubstituted N-hydrogen radicals According to thismodification one may treat a carrier starting material which containsboth N- chloro radicals and N-hydrogen radicals with a bromide toreplace the chlorine atoms with bromine. Thusfor. example one may reactN-monochloro-S-substituted hydantoins with an equivalent of a bromidesuch as sodium bromide to produce an N-monobromo-S-substituted hy-.dantoin. It will be noted that in this particular. embodiment, as wellas the foregoing broad process wherein all of the N-chlororadicals arechanged to N-bromo, radicals, all of the bromide reactant is utilized toproduce a bromine carrier compound. It is also apparent that bythismodification one may produce N-bromohalogenating agents under mildreaction conditions characterized by the absence of strong reagents suchas elementary bromine. or alkali.

The following examples will illustrate the foregoing embodiments of theprocess of the present invention:

Example 1 103 grams of sodium bromide were dissolved in 200 millilitersof water. To this were added, with agitation,

134 grams of N-chloro succinimide; Stirring was continned for 15minutes, at'which time the N-bromo-succinimide wasfiltered 'ofi, washedfree of sodium chloride, and dried. It weighed 169 grams, analyzed 44.6%active bromine, and had a melting :point of 173- C.

Example 2 Example 3 The N-chlorinated carrier may also be used inconjunctionwith elementary bromine to make available all the bromineadded to the process. In this method of manu facture, the; carrier, istreated with bromine and sufficient alkali to take, up the. hydrogenbromide. The.correspond-.- ing. .N-chlorinated carrier is then.. added'to displace, fthfix bromine from.=the by-product .bromine;salt. Thusz.

12,8-ij.gramsof1 5,-5-dimethyl, hydantoin-1 were dissolved TheaboveE'quations 3 and 4 illustrate the sequenceof: the reaction whichmay be described in its overall aspects according to the followingequation:

It is also contemplated as an embodiment of thepresent.

invention, theprovision of a process for producing N bromo-N-chlorohalogen carriers by reacting an..N- chloro carrier compound of thecharacter previously described with a bromide.

bromo halogenating agents.

carrier containing at least 2-N-chloro radicals with .a bromine salt. IThe amount of bromide required. ,to produce ,these mixed chloro-bromohalogen. carriers is. less...

thanthat which is requiredfor complete replacementof all-of the N-chlorosubstituents. Thus, for. example; by reacting. a mole ofN,N-dichloro-5-substituted hydantoin with one equivalent of a bromidesuch as KBr, a mixed chloro-bromo hydantoin is produced- Generally theamount of bromide required to carry out this reaction may vary but inall cases it will be less than an amount which:

would be required to completely substitute all of the N- chlorosubstituents. It is also possibleto prepare .N-chloro-N-bromo-N-hydrogen carrier compositions byteacting a carriermolecule which contains at least. three available irnide groups of whichonly two are chlorinated.

Thus, for example, one may react N,N-dichloro cyanuric acid Withsodiumbromide to produce N-chloro-N-bromo cyanuric acid.

The following examples will illustratethe various.-.em bodiments oftheprocess, of the present inventionas .ap-% plied to making mixedchloro-bromo halogenatingagentsfrom ,N-chloro starting materials.

Example '4 273 grams of N-,N,N.-trichloro-3a,6a dimethyl'glyLacolurihwere' suspended inwater; to form :a heavy: slurryz It hasbeenfound that by a modification of the broad process one may obtainthese mixed chloro-bromo carrier compounds by utilization.of the broadconcepts disclosed for the production .of .N-

Generally to prepare thesemixed halogen carriers one reacts an N-chloro.halogen.

To this were added 533 grams of a crude concentrated solution of alkaliand alkaline earth bromides analyzing 30% bromine. When all the brominehad been taken up,

the slurry was filtered oil, washed and dried. The product consisted ofN-chloro-N,N-dibromo-3a,6a-dimethyl glycoluril. It contained theoreticalamounts of active halogen.

Example 5 To a solution containing 119 grams of potassium bromide, 211grams of N,N-dichloro-S-ethyl-S-methyl hydantoin were added withconstant agitation. The resultant product, after filtering, washing anddrying, weighed 245 grams and contained 31.7% bromine and 14% chlorrne.

Example 6 232 grams of N,N,N-trichloro-cyanuric acid were added withconstant agitation to a solution of 103 grams of sodium bromide in 1liter of water. When the bromine had been completely taken up, theproduct was removed on a filter, washed and dried. It consisted ofN,N-dichloro-N-bromo-cyanuric acid, and contained theoretical amounts ofthese halogens.

Another embodiment of the process of this invention is the provision ofa process for preparing admixtures of N-chloro N-bromo halogen carrierswith N,N-dihalo halogen carriers, wherein the dihalo materials containeither chlorine or bromine. For example, referring specifically to5-substituted hydantoins it is contemplated that admixtures of anN-chloro-N-bromo-S-substituted hydantoin with either an N,N-dichloro oran N,N-dibromo-S-substituted hydantoin may be prepared by reacting anN,N-dichloro-S-substituted hydantoin with a bromine salt. The amount ofbromide required will vary with the particular end product desired. Forexample, to prepare the mixed dihalo with N,N-dichloro less than oneequivalent of a bromide per mole of N,N-dichloro hydantoin startingmaterial is required. Thus the bromide forms mixed chloro-bromohydantoin and to the extent that the bromide utilized is less than anequivalent per mole of starting material, there remains unreactedN,N-dichloro-S-substituted hydantoin present in the admixture.Similarly, if one reacts more than one equivalent but less than twoequivalents of a bromide with a mole of N,N-dichloro-S-substitutedhydantoin, an admixture of N-chloro-N-bromo-S-substituted hydantoin withN,N-dibromo-S-substituted hydantoin will be formed to the extent thatthe bromide exceeds one equivalent per mole of starting material. Othermixed halogen carriers may also be prepared by a modification of thisprocess, it merely being required that less than the stoichiometricamount of bromine salt be reacted with the N-polychloro startingmaterial. Thus for example to prepare such an admixture usingN,N,N-.trichloro-cyanuric acid one would utilize a bromide in an amountranging from less than one equivalent to somewhat less than threeequivalents per mole of starting material, the stoichiometric amountrequired for complete bromination being at least three equivalents permole of trichlorocyanuric acid. The following examples will illustratethe above described modification.

Example 7 To an aqueous slurry of 197 grams of N,N-dichloro-5,5-dimethylhydantoin is added with constant stirring 51.5 grams ofNaBr. After addition is complete the resultant product is recovered byfiltration, washing and drying. The product is an admixture of equalparts of N,N-dichloro-5,5-dimethyl hydantoin and N-bromo-N-chloro-5,5-dimethyl hydantoin.

I Example 8 To a slurry of 197 grams of N,N-dichloro-S,S-dimethylhydantoin in water is added 154.5 grams of NaBr while maintainingconstant stirring. The resultant product is recovered by filtration,washed with water and dried. The

types of what might aptly be termed 'multi-halogenated" substitutedhydantoins can exist, and can be made by the methods herein described.The bromine may be attached to the nitrogen atom in the .1-positionwhich is vicinal to the S-Substituted carbon atom,or may be attached-tothe nitrogen atom in .the 3-position. Thus there may beN-lbromo-N-3-chloro, or N-1-chloro-N-3-bromo compounds. It has not beendefinitely established that the N-chloro-N- bromo compounds produced inaccordance with the herein described methods are not mixtures of suchisomers. In the subjoined claims, both types of chloro-bromo orbromo-chloro products are claimed.

It is a particularly preferred embodiment of the present invention toutilize S-substituted hydantoi'ns and 3a,6a substituted glycolurils asstarting materials. Thus, with reference to the S-substituted hydantoin,the radicals on the carbon atom in the number 5 position are given inthe examples as being methyl, dimethyl, methyl-ethyl, ethyl, phenyl,diphenyl, or the like. It is to be understood that considerablevariations are possible in the substituents in the number 5 position,and compounds such as 5,5-dipropyl, 5,5-phenyl, ethyl may be prepared.Combinations of aliphatic and aromatic radicals containing up to about10 carbon atoms in eachof the respective radicals are contemplated aspreferred starting materials, as is disclosed in my copendingapplication, Serial No. 593,047, filed June 22, 1956.

With respect to 3a,6a-substituted glycolurils it is preferred that thesesubstituents be of the same character as those substituents in thenumber 5 position of the hydantoin starting materials, but for the sakeof economy it may be desirable to use only the methyl or ethylsubstituted N-chloro-glycolurils.

In summary, it is apparent that the process of the present invention isbroadly applicable to the production of N-brominated halogenation agentsspecifically characterized as being prepared by bromination of N-chloroorganic nitrogen compounds containing at least one radical selected fromthe group consisting of:

01 0 Cl 0 G10 01 l IH 0 Cl 0 ilhlm, ail-2L, SO.NH, 4): -('3l I" and C 0Cl Mail-11am Exemplary of compounds containing such groups or radicalsare N,N-dichloro-S-substituted hydantoins, N-chlorosuccinimide,N-chloro-acetamide, N-chloro-phthalimide, N-chloro-cyanuric acids,N-chloro-toluene-sulfonimides, N-chloro-melamines,N-chloro-S-substituted barbiturates, N-chloro-3a,6a-substitutedglycolurils, and the like.

While several particular embodiments of this invention are shown above,it will be understood, of course, that the invention is not to belimited thereto, since many modifications may be made, and it iscontemplated, therefore, by the appended claims, to cover any suchmodifications as fall within the true spirit and scope of thisinvention.

I claim:

1. A process for preparing N-brominated halogen compounds whichcomprises treating an N-chlorinated compound selected from the groupconsisting of N,N-dichloro-5-lower alkyl substituted hydantoins,N-chloro succi'nimide, N-chlorinated cyanuric acids, N-chlorinatedmelamines, and N-chlorinated-3a,6a-lower alkyl substituted glycolurilswith at least about 0.5 equivalent of an inorganic bromide selected fromthe group consisting of sodium bromide, potassium bromide, calciumbromide and 8 'mixtures-zthereof, .per mole of: N-chlorinated; compound.References Cited inzthefile of patent I2; pmcessnf'claim :1wheIeim-saidshlorjuated.compound is an N,N-dichloro-5-lower alkylsubstituted -hy- UNITED STATES PATENTS dantoin: 2,779,764 Patterson Jan.29, 1957 '3: The process of claim v1 .whereinssaid chlorinated com- 5pound. is an Nfchlorinatedcyanuric acid. OTHER REFERENCES 4. The processofclaim 1 whereinsaid:chlorinated'com- Chattaway t aL; Journ l f th Chmi l Society. pound .is an N-ch1orinated-3a,6a-l0wer :alkyl substituted(1902), l, 81, pages 200-202, glycoluril.

1. A PROCESS FOR PREPARING N-BROMINATED HALOGEN COMPOUNDS WHICHCOMPRISES TREATING AN N-CHLORINATED COMPOUND SELECTED FROM THE GROUPCONSISTING OF N, N-DICHLORO-5-LOWER ALKYL SUBSTITUTED HYDANTOINS,N-CHLORO SUCCINIMIDE, N-CHORINATED CYANURIC ACIDS, N-CHLORINATEDMELAMINES, AND N-CHLORINATED-3A, 6A-LOWER ALKYL SUBSTITUTED GLYCOLURILSWITH AT LEAST ABOUT 0.5 EQUIVALENT OF AN INORGANIC BROMIDE SELECTED FROMTHE GROUP CONSISTING OF SODIUM BROMIDE, POTASSIUM BROMIDE, CALCIUMBROMIDE AND MIXTURES THEREOF, PER MOLE OF N-CHLORINATED COMPOUND.